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Cardiac Stem Cell Therapy Clinical Experiences

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Harry and Shelley Page Professor of Medicine. in ... VEGF, bradykinin, adenosine, serotonin. Sonicated microbubbles. Prolong intracoronary dwell time ... – PowerPoint PPT presentation

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Title: Cardiac Stem Cell Therapy Clinical Experiences


1
Cardiac Stem Cell TherapyClinical Experiences
  • David Zhao, MD, FACC, FSCAI
  • Harry and Shelley Page Professor of Medicine
  • in Interventional Cardiology
  • Director, Cardiac Catheterization Laboratory
  • Interventional Cardiology
  • Vanderbilt University Medical Center
  • Nashville, TN USA

2
Mending a Brocken HeartA Real Challenge in
Medicine
  • Acute MI 7,200,000
  • New cases 865,000/y
  • Mortality 221,000/y
  • CHF 5,000,000
  • New cases 550,000/y
  • Mortality 57,218/y
  • Transplant 2,016/y

Regenerate a new heart dream comes true!?
3
Cell Based Cardiac Regeneration
  • Intracoronary infusion
  • Coronary artery
  • Coronary vein
  • Direct intramyocardial injection
  • Epicardial (Surgery)
  • Endocardial (Percutaneous)
  • Intravenous infusion
  • Systemic growth factors
  • Tissue-engineered constructs

4
Cell Based Cardiac RegenerationIntracoronary
Injection
  • Advantages
  • Allow homogeneous homing of cells into target
    zone
  • Easy delivery
  • Disadvantages
  • Risk of induce myonecrosis
  • Low cell homing due to rapid coronary transit and
    barriers.

5
Cell Based Cardiac RegenerationIntracoronary
Injection
CCTRN TIME Late TIME Trials PI David Zhao
6
6 and 18 mon Results from BOOST
N60
Stem Cell
Controls
?EF
6.7 5.9
6 Mon 18 Mon
0.7 3.1
plt0.05 p0.27
Meyer et al, Cir 20061131272
7
TOPCARE-AMI
N28
Continuous improvement in EF at 4 and 12 Mon
JACC 2004441690
8
REPAIR-AMI Change in LVEF Endsystolic Volume
EF
ESV
Schachinger et al NEJM 20063551210
9
Post MI EF and Benefit
Schachinger et al NEJM 20063551210
10
BMC Modifies LV RemodelingInteraction Between EF
and ES Volume
11
REPAIR-AMI 2Year Follow Up
12
Problems and Potential Solutions
  • Problems
  • Rapid coronary transit
  • Endothelial barrier
  • Increase coronary permeability
  • VEGF, bradykinin, adenosine, serotonin
  • Sonicated microbubbles
  • Prolong intracoronary dwell time
  • Coronary vein occlusion
  • Selected coronary artery occlusion
  • Increase intracapillary pressure
  • Aortic and pulmonary artery occlusion
  • Pressured perfusion
  • Retrograde perfusion

13
Cell Based Regeneration Endomyocardial Injection
  • Advantages
  • Small number of cells required
  • Localized delivery
  • Disadvantages
  • Leads to islands of cells
  • Complex delivery system
  • High cell death due to tissue hypoxia and
    physical stress

14
Cell Based Cardiac RegenerationEndomyocardial
Injection
NOGA System
CCTRN FOCUS Trial PI Zhao
15
Chronic Ischemia Cardiomyopathy6 months Results
from PROTECT-CAD
N28
Stem Cell
Controls
ETT EF Ischemia
?20.9 ?7.6 ?31
p0.026 plt0.01 p0.04
?18 ?4.6 ?26
ACC 2006
16
Cell Based Cardiac RegenerationEpicardial
Intramyocardial Injection
LIMA
17
Cell Based Cardiac Regeneration Intravenous Cell
Infusion
  • Advantages
  • Simple and least invasive
  • Disadvantages
  • Limited cell number to home target area
  • Homing to non-cardiac organs

18
IV Infusion PROVACEL Trial
Joshua Hare NY Cell Synposium 2008
19
Cell Based Cardiac Regeneration Systemic Growth
Factors
  • Advantages
  • Simple and least invasive (GCSF)
  • Disadvantages
  • Limited cell number to home target area
  • Cell homing to non-cardiac organs
  • Potential negative effects on restenosis and
    malignancy

20
Systemic GCSF Infusion after Acute Myocardial
Infarction
Zohlnhofer, JACC in press
21
Cell Based Cardiac RegenerationTissue
Engineering Constructs
  • Advantages
  • Plasticity of implanted cells
  • Permanent release of effective substrates
  • Selective cell types and functions
  • Disadvantages
  • Complex delivery system
  • Potential oncogenic effects

22
Cardiac Cell Therapy Savior for the Dying
Heart!?
  • Mechanisms underlining cardiac regeneration are
    largely unknown
  • Clinical outcomes are modest at the best
  • Ethics in embryogenic cell research are
    controversial

One small step for man, one giant leap for
mankind Neil Armstrong, Apollo 11, 7/1969, lunar
landing
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